Nausea and vomiting are common, distressing side effects associated with chemotherapeutic regimens, resulting in reduced quality of life and treatment adherence. Appropriate antiemetic prophylaxis strategies may reduce/prevent chemotherapy-induced nausea and vomiting (CINV). Historically, investigators assessed antiemetics up to 120 hours after chemotherapy. However, CINV can extend beyond this time. Thus, the effect of antiemetics during the long-delayed period (>120 hours) requires investigation. Emerging treatment options, including certain antibody-drug conjugates (ADCs), are associated with high rates of acute and late-onset nausea and vomiting that can last for extended duration. With the increasing number of ADCs approved and in development, there is urgency to control nausea and vomiting in patients receiving these new therapies. In this narrative review, we present the emetogenic potential of ADCs and CINV in the long-delayed period along with antiemetic prophylaxis strategies used to date. We also discuss the promising role of the fixed-combination antiemetic NEPA ([fos]netupitant plus palonosetron) in controlling long-delayed nausea and vomiting, addressing characteristics that may contribute to its longer efficacy duration compared to other antiemetics. Finally, we highlight encouraging results with NEPA in patients receiving the ADCs trastuzumab deruxtecan or sacituzumab govitecan, which suggest NEPA may be an effective antiemetic prophylaxis in these settings.